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Metabolic Profiling to Determine Bactericidal or Bacteriostatic Effects of New Natural Products using Isothermal Microcalorimetry
Published on: October 29, 2020
An alternative sterility assessment for parenteral drug products using isothermal microcalorimetry
D Brueckner1,2, S Krähenbühl3, U Zuber2
1Center of Biomechanics and Biocalorimetry, University of Basel, Allschwil, Switzerland.
Aims:
Production and release of injectable drug solutions are highly regulated since the administration of injectables bypasses natural body barriers. The sterility test is the last opportunity of product quality assessment. However, sterility is currently assessed by visual inspection (VI) that is time consuming and somewhat subjective. Therefore, we assessed isothermal microcalorimetry (IMC) as a replacement for the VI of the filtration based state-of-the-art sterility control.
Methods And Results:
We used ATCC strains and house isolates to artificially contaminate frequently produced monoclonal antibodies (Avastin, Mabthera, Herceptin). After filtration, growth was assessed with IMC. Growth of all micro-organisms was reliably and reproducibly detected 4 days after inoculation, which was significantly faster than with VI.
Conclusions:
The reliability and the sensitivity of IMC have a large potential to improve sterility controls. Further evaluation of this alternative method is therefore highly recommended.
Significance And Impact Of The Study:
Drug safety is of great concern for public health. Faster and safer drug production could be achieved using the technique described here. All the tests were performed with real manufactured drugs and complied with pharmaceutical standards. This suggests that drug sterility testing can be improved with potentially increased safety and cost reduction.
Insights
Isothermal microcalorimetry (IMC) offers a faster and more reliable method for sterility testing of injectable drugs compared to traditional visual inspection (VI). This advanced technique improves drug safety and production efficiency.
Area of Science:
- Pharmaceutical Science
- Biotechnology
- Analytical Chemistry
Background:
- Injectable drug production requires stringent quality control due to bypassing natural body barriers.
- Sterility testing is a critical final quality assessment step for injectable products.
- Current visual inspection (VI) methods for sterility testing are time-consuming and subjective.
Purpose of the Study:
- To evaluate isothermal microcalorimetry (IMC) as a replacement for visual inspection (VI) in sterility testing.
- To assess the efficacy of IMC for detecting microbial growth in injectable drug solutions.
- To compare the speed and reliability of IMC against traditional VI methods.
Main Methods:
- Artificially contaminated monoclonal antibody solutions (Avastin, Mabthera, Herceptin) with microbial strains.
- Utilized filtration-based methods for sample preparation.
- Assessed microbial growth using isothermal microcalorimetry (IMC) after inoculation.
Main Results:
- Isothermal microcalorimetry (IMC) reliably detected microbial growth in all tested samples.
- Detection of microbial growth occurred within 4 days, significantly faster than visual inspection (VI).
- Results were reproducible and demonstrated high sensitivity for sterility assessment.
Conclusions:
- IMC shows significant potential to enhance the reliability and sensitivity of sterility controls for injectable drugs.
- IMC offers a faster and potentially safer alternative to visual inspection for drug sterility testing.
- Further evaluation of IMC is recommended for pharmaceutical applications, potentially leading to cost reductions.
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